Left ventricular hypertrophy (LVH) is very common, is a strong independent predictor of major adverse cardiovascular (CV) events and mortality, and has a large attributable population risk. Regression of LVH may reduce subsequent CV events and death, potentially independent of BP. However, several critical questions remain before LVH can be established as an independent therapeutic target primarily, and the critical links between hypertension treatment, LVH regression, and reduction in CV events are not well understood. The upcoming, NHLBI-funded SPRINT study is a unique, time-limited opportunity to efficiently and cost-effectively address these important questions. SPRINT will be a controlled clinical trial to determine whether intensively reducing systolic BP to <120 mmHg will reduce CV events compared to standard control (BP <140 mmHg). The proposed SPRINT-HEART ancillary study is highly responsive to RFA HL10-024 and innovatively assembles an ideal combination of resources: the latest cardiovascular magnetic resonance imaging (CMR) techniques, 5 well-suited clinic sites, a novel intervention, and a large randomized clinical events trial. It will enroll 340 participants from SPRINT (170 each group) and measure LV mass and enddiastolic volume (EDV) at baseline and at 18-month follow-up to address the following primary hypothesis: Hypothesis: At 18-month follow-up the intensive BP reduction group will have reduced LV mass and improved LV remodeling compared to standard control. The study will also determine the relationship of LV mass and EDV with the CV composite endpoint in SPRINT during follow-up (mean 3.4 years) to examine the following secondary hypothesis: The improvements in LV mass and remodeling will be associated with reductions in CV events. As an exploratory aim, the change frombaseline to 18-month follow-up in LV strain, myocardial fibrosis, left atrial volume, and aortic stiffness will be measured in the intensive BP reduction and standard control groups. This will enable the study to explore potential mechanisms whereby intensive BP reduction, in the range being tested in SPRINT, influences LVH and CV events. By determining the responses of these more novel CMR measures to intensive BP reduction, it will also lay the groundwork for their potential inclusion in future trials. Finally, the study will examine the relationships between the 18-month changes in CV structure and function in subgroups of particular interest including those with prior CV disease; those > 75 years old, and those with chronic kidney disease. SPRINT-HEART will test critical hypotheses that would not otherwise be addressable, challenge existing paradigms, overcome limitations of prior studies, provide key mechanistic information to help interpret the SPRINT results, and advance our understanding of LVH and its management PUBLIC HEALTH RELEVANCE: Left ventricular hypertropy (LVH) is common in the general population and is a strong independent predictor of cardiovascular (CV) events, including heart attack, heart failure, and death. However, the optimal level of blood pressure control (BP) needed to prevent or reduce LVH is unknown, and the extent to which LVH should be targeted independently of BP is not clear. SPRINT-HEART is an innovative and cost-effective approach to advance our understanding of the mechanistic links between BP treatment, cardiac structure and function, and CV events. (End of Abstract)